HISTORIC 415 



the precipitate. This explanation naturally had the effect of leading 

 many to assume that the Bordet-Gengou phenomenon of complement 

 fixation may be the result of a similar precipitation process, and led to 

 many interesting and valuable investigations, especially those made by 

 Gay. It is now generally agreed, however, that protein amboceptors 

 are formed, and that actual complement fixation occurs independently 

 of precipitation. Later Neisser and Sachs elaborated on Gengou's 

 studies, and perfected a complement-fixation technic for the differen- 

 tiation of proteins that is much more delicate than the precipitin test, 

 and serves to demonstrate and differentiate traces of protein, as in 

 blood-stains, so minute in quantity as not to be appreciable by the 

 precipitin test. 



Widal and Lesourd applied the Bordet-Gengou reaction to the 

 diagnosis of typhoid fever, using an emulsion of typhoid bacilli and the 

 serum of a typhoid-fever patient, and found that a positive reaction 

 occurred more frequently and earlier than the agglutination test. These 

 observations were made soon after Bordet and Gengou's discovery, and 

 were probably the first direct and practical application of a complement- 

 fixation technic in diagnosis. It was not until several years later, 

 however, that the possibilities of the method were seriously considered. 



Hitherto most experiments were conducted with known antigens and 

 their antibodies. It was shown, especially in the work of Neisser and 

 Sachs on protein differentiation, that when an antigen and its specific 

 antibody are present complement is absorbed, and the specific relation 

 existing between these bodies was again emphasized. Hence in a com- 

 pkment-fixation test, if the antibody is known the antigen may be found, 

 or if the antigen is known the antibody may be found, the detection in either 

 instance depending upon whether or not complement is absorbed, this being 

 decided by adding corpuscles and their amboceptors to the mixture, the 

 absence or the occurrence of hemolysis determining this point. In this 

 manner Neisser and Sachs were able to diagnose the nature of blood- 

 stains by using solutions of the suspected stains as antigen, and adding, 

 in different experiments, known antiserums secured by injecting rabbits 

 with various bloods. When a positive complement-fixation reaction 

 occurred, they concluded that the antigen of the blood corresponded to 

 the known antibody, and they were thus able to identify the species of 

 animal from which the blood in the stain was derived. 



Wassermann and Sachs, encouraged by these results, endeavored, 

 by complement-fixation tests, to show the existence of antigens in dis- 

 eased organs, using tuberculous glands and lungs with an antituberculous 



